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Innate Immunity > Macrophages > Flashcards

Macrophages Flashcards

(51 cards)

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1
Q

Haematopoiesis is?

A

Haematopietic stem cells found in bone marrow of adults differentiate into various cells

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2
Q

Features of HSCs

A

Sustain blood cells throughout life

Capable of self-renewal

Multipotent - stem cells generate other cells of multiple lineages

Two main lineages generated are lymphoid and myeloid cells

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3
Q

Determining factors for Cells produced by HSC

A

Cellular environment

Transcription factors

Soluble mediators in the environment

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4
Q

How does Pattern Associated Molecular Patterns(PAMPs) help microbe recognition

A

PAMP receptors recognise PAMPs
Works on principle there is difference between cell and pathogenic cells

PAMP also recognised indirectly

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5
Q

Examples of Bacterial PAMPs

A

Cell wall components

Such as LPS and LTA

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6
Q

Examples of viruses PAMPs

A

ssRNA and dsRNA that form part of viral life cycle

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7
Q

Examples of yeast PAMPs

A

Sugars

B-glucans

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8
Q

Examples of helminths PAMPs

A

Sugars e.g Chitin

Proteins

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9
Q

Where are PRRs encoded?

A

Germline encoded in genes for multicellular organisms

Highly abundant in cells of innate immune response
- phagocytes(macrophages neutrophils and dendritic cells)

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10
Q

Where are PRRs located

A

Soluble
Exposed on cell surface
In cytoplasm
In vacuoles

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11
Q

What are Toll Like Receptors

A

Best characterises PRRs

Recognise wide range of pathogens which lead to appropriate signalling and responses

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12
Q

How many TLRs are there

A

10

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13
Q

What is TLR1

Ligand and target microbes

A

Triacyl lipopeptides

Mycobacteria

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14
Q

What is TLR2
Ligand

Target microbes

A

Peptidoglycans - Gram positive bacteria

GPI-linked proteins - Trypanosomes

Lipoproteins - mycobacteria

Zymosan - yeasts and other fungi

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15
Q

What is TLR3 ligand and target microbes

A

dsRNA - Viruses

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16
Q

What is TLR4 ligand and microbes?

A

LPS - Gram-negative bacteria

F-protein - Respiratory Syncytial virua

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17
Q

What is TLR5 ligand and microbe

A

Flagellin - bacteria

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18
Q

What is TLR6 ligand and target microbes

A

Diacyl lipopeptides - mycobacteria

Zymosan- yeast and other fungi

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19
Q

What is TLR7 and TLR8 ligand and target microbes?

A

ssRNA - Viruses

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20
Q

What is TLR9 ligand and target microbes?

A

CpG unmethylated dinucleotides and dinucleotides - Bacterial DNA

Herpesvirus infection - Some herpesviruses

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21
Q

What are the major classes of PRR besides TLR’s and what they bind to?

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A

Dectin-1 Receptors binds to B-glucans

Mannose receptor bind to mannose

Scavenger receptor bind to lipids/proteins

22
Q

Major roles of macrophages

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A

Pattern recognition
Phagocytosis
Killing infected cells
Cytokines release

Direct both innate and adaptive immune response through secretion of cytokines and chemokines plus antigen presentation to T cells

23
Q

Where do Macrophages derive

Where are macrophages found

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A

HSC from myeloid lineage
Myeloid precursor bone marrow cells

Macrophages found in all tissues within body

24
Q

What cells have myeloid precursors

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A

Neurtrophils
Monocytes
Macrophages

25
What is role of Monocytes
Released into circulation so can enter tissues and replace resident tissue macrophages
26
What control myeloid differentiation
Sequential TFs Soluble mediators Micro-environmental factors
27
What are tissue resident macrophages?
Macrophages that establish in tissue during early embryogenesis to produce resident cells that proliferate Have different expression patterns that can be analysed by microarray
28
What are DAMPs
Damage associated molecular patterns from stressed cells and allow recognition of healthy cells from damaged cells Usually from contents of damaged cell spilling out.
29
Macrophages integrate a large number of stimuli which result in different types of activation Why?
Enhances effector functions and ensure a directed and appropriated response
30
How does classically activated macrophage work?
Tissue macrophage recognises e.g LPS with TLR or IFNy released by cells when they recognise viruses This causes differentiation of macrophage into a classically activate macrophage
31
How can you recognise a classically activated macrophage?
Surface markers and phenotypic features E.g. Lots of MHC Class II on the surface Produce many antimicrobials E.g. Hydrogen peroxide, nitric oxide Th1 cytokines IL-6, IL-23 leads to Th17 cells
32
What are wound healing macrophages What do they do and how
Macrophages that cause tissue damage repair Produce precursors of collagen for tissue By Increasing transcription and translation of arginase which will convert to arginine to ornithine a precursor for polyamide an collagen for matrix regeneration Increase apoptosis
33
What activates Wound healing macrophages
Inflammatory cytokines or Th2 cytokines such as IL4
34
How can pathogens skew wound healing macrophages
M.tb increases arginase production for survival
35
What are Regulatory Macrophages?
For parts like eyes,brain and tested where we do not want excessive inflammatory response to prevent excess damage Anti-inflammatory Macrophages produce anti-inflammatory cytokines IL-10, TGF-B to calm down response
36
What are Tumor associated macrophages? And how do they work?
Macrophages are hijacked by tumors Found in tumors Differentiate to produce environment beneficial for tumour E.g increase VEGF to increase vascularise to tumour cells to encourage growth Suppress immune response so tumours not killed. Produce growth factors to encourage tumour development Macrophage normally indicate poor prognosis for tumours
37
Macrophages recognise pathogen via
Directly or opsonic Receptors
38
What is phagocytosis
Main mechanism for uptake and destruction of microbes and apoptosis cells
39
Three major steps of macrophage phagocytosis
Initial recognition (receptor mediated) Uptake, signalling and actin-driven cytoskeletal remodelling Processing-killing, presentation or non inflammatory removal
40
Name pathogens that evade phagocytosis
Yersinia, salmonella, clostridium toxins that block Rho-family of GTPases
41
How does uptake via opsonic phagocytosis work?
Particles coated in complement or soluble pattern recognition Receptors (MBL, collections,MFG-8) or antibodies Receptors recognise coated pathogens and phagcytose it E.g. Binding by FC receptor and zipper hypothesis
42
What are main Fc Receptors?
FcyRI( CD64) has high affinity to momomeric IgG FcyRIIandRIII(CD32 and 16) -- low affinity -- polymeric IgG
43
Stages of phagocytosis
Ligand binding Activation of phagocytic cell Engulfment Internalisation /fusion with lysosomes
44
How does phagosome maturation progress
Phagosome matures and gradually acidified via fusion with lysosomes from endocytic pathway Rab protein 5,7,11 essential for vesicular fusion Final degradation through generating phagolysosome Pathogen components either presented on surface to initiate further immune response or degraded in cell
45
What pathogen blocks phagolysosome formation
M.tb by inhibiting sphingosine kinase signalling
46
Autophagy how it occurs And what is it
Initiated via starvation or stress from viral infection Cell packages cut solid contents in double membrane vehicle and delivers to lysosomes for degradation Growing evidence cells use same machinery against invading microorganism
47
Killing mechanisms of macrophages ?
Reactive oxygen species/ reactive nitrogen species Proteolytic and hydrolytix enzymes -e.g proteases Antimicrobial peptides Nutrient deprivation
48
What are antimicrobial peptides?
Defensins and cathelicidins -short peptides, between 12 and 50 aminonacids Positively charges and bind electrostatically to form multimeric pores killing microbes Also act as chemoattractants
49
What increases acidity in phagosmal maturation
Acidity increased via V-ATPase
50
Name hydrolytic enzymes
Lysozymes, cathespin D, lipases
51
What does the deprivation of nutrients macrophage kills mechanism?
IDO metabolise tryptophan Arginase metabolises arginine Vitamin B12 binding protein and lacroferrin being B12 and iron

Innate Immunity (5 decks)

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